Acute renal failure associated with vancomycin and β-lactams for the treatment of osteomyelitis in diabetics: piperacillin–tazobactam as compared with cefepime

Few data are available on the nephrotoxic potential of vancomycin when combined with certain β-lactam antibiotics for the treatment of osteomyelitis (OM). A retrospective cohort study was conducted of all diabetic patients with OM treated with vancomycin plus piperacillin–tazobactam (VPT) or vancomycin plus cefepime (VC) for at least 72 h at a VA Medical Center between 1 January 2006 and 31 December 2011. All patients with a creatinine clearance (CrCl) of ≤40 mL/min, a blood urea nitrogen/serum creatinine (SCr) ratio of ≥20 : 1 or an absolute neutrophil count of <500 cells/mm³ were excluded. The primary outcome was development of acute renal failure (ARF), defined as an increase in SCr of 0.5 mg/dL or 50% of baseline. One hundred and thirty-nine patients met the inclusion criteria; 109 in the piperacillin–tazobactam group and 30 in the cefepime group. Among patients receiving VPT, 29.3% (32/109) developed ARF, as compared with 13.3% (4/30) receiving VC (p 0.099). Among patients receiving high-dose therapy (≥18 g of piperacillin–tazobactam daily or ≥3 g of cefepime daily), 37.5% (9/24) receiving VPT and 17.6% (3/17) receiving VC developed ARF (p 0.29). A multiple logistic regression analysis identified weight and average vancomycin trough as the only significant predictors of ARF; the choice of VPT as therapy yielded an OR of 3.45 (95% CI 0.96–12.40; p 0.057). The authors were unable to detect a statistically significant difference in ARF between groups; however, the power requirement was not met. Further study with a larger patient population seems warranted.     

Chemo-Radiotherapy in Locally Advanced Squamous Cell Carcinoma of the Head and Neck: Factors Affecting Toxicity Patterns

Abstract

Radiation and chemotherapy in the treatment of locally advanced squamous carcinoma of the head and neck can be used according to different strategies: concomitant, alternation, consecutive. The limiting acute toxicity is local with the radiosensitizing capacity of the drug and type of radiation fractionation being the predominant factors. Regimens providing more that 50% of complete responses are usually associate with a more than 40% incidence of severe local reaction. More information is needed on late toxicity that influences the quality of life for these patients.     

The dynamic triple peak impact factor in traumatic brain injury influences native protein structures in gray and white matter as measured with computational simulation

Abstract

Background: Traumatic brain injuries (TBIs) cause a substantial burden to the patient, relatives, and the society as a whole. Much experience and knowledge during the last two decades have improved the neurosurgical treatment as well as the outcome. However, there is still much debate on what actually happens when external kinetic energy is transferred to the head immediately after a TBI. Better knowledge about the cascades of mechanical events at the time of accident is a prerequisite to further reduce the burden in all categories and improve the neurosurgical care of TBI patients.

Methods: In the present study, we use the finite element modeling of the human brain to numerically simulate impact velocities of 10, 6, and 2 m/s to clarify some of the immediate consequences of the external kinetic energy transfer focusing on the gray (GM) and white matters (WM).

Results: The numerical simulation was focused on the external kinetic energy transfer with a level of 227·3 J reaching the head, intracranial pressure (ICP), strain energy density, 1st principal strain level, and their respective impacts on the brain tissue. The results show that, for a 10 m/s impact, a total internal potential energy of 208·6 J was absorbed, of which 14·3% (29·81 J) was absorbed by the scalp, 22·05% (46·0 J) by the outer compact bone, 17·12% (35·72 J) by the porous bone, 27·44% (57·23 J) by the inner compact bone, and 7·31% (15·24 J) by the facial bone. The rest of the internal potential energy was defined to reach the GM (3·6%, 7·51 J) and the WM 1·59% (3·31 J). Also, the ICP, strain energy density, and 1st principal strain levels, defined as the dynamic triple peak impact factor, influenced the GM and WM with their own impact peaks during the first 10 ms after the accident and were the highest for the 10 and 6 m/s impacts, while the 2 m/s impact had only a slight influence on the GM and WM structures.

Conclusions: The present study shows for the first time that following an impact of 10 m/s, 88·31% of the calculated external kinetic energy was absorbed by the external parts of the head before the remaining energy of 5·19% reached the GM and WM. GM absorbed about twice as much of the energy compared to the WM. It is suggested that the dynamic triple peak impact factor may have a profound effect on native protein structures in the cerebral metabolism after a TBI.     

Cognitive deficits develop 1 month after diffuse brain injury and are exaggerated by microglia-associated reactivity to peripheral immune challenge

Traumatic brain injury (TBI) elicits immediate neuroinflammatory events that contribute to acute cognitive, motor, and affective disturbance. Despite resolution of these acute complications, significant neuropsychiatric and cognitive issues can develop and progress after TBI. We and others have provided novel evidence that these complications are potentiated by repeated injuries, immune challenges and stressors. A key component to this may be increased sensitization or priming of glia after TBI. Therefore, our objectives were to determine the degree to which cognitive deterioration occurred after diffuse TBI (moderate midline fluid percussion injury) and ascertain if glial reactivity induced by an acute immune challenge potentiated cognitive decline 30 days post injury (dpi). In post-recovery assessments, hippocampal-dependent learning and memory recall were normal 7 dpi, but anterograde learning was impaired by 30 dpi. Examination of mRNA and morphological profiles of glia 30 dpi indicated a low but persistent level of inflammation with elevated expression of GFAP and IL-1β in astrocytes and MHCII and IL-1β in microglia. Moreover, an acute immune challenge 30 dpi robustly interrupted memory consolidation specifically in TBI mice. These deficits were associated with exaggerated microglia-mediated inflammation with amplified (IL-1β, CCL2, TNFα) and prolonged (TNFα) cytokine/chemokine expression, and a marked reactive morphological profile of microglia in the CA3 of the hippocampus. Collectively, these data indicate that microglia remain sensitized 30 dpi after moderate TBI and a secondary inflammatory challenge elicits robust microglial reactivity that augments cognitive decline.Statement of SignificanceTraumatic brain injury (TBI) is a major risk factor in development of neuropsychiatric problems long after injury, negatively affecting quality of life. Mounting evidence indicates that inflammatory processes worsen with time after a brain injury and are likely mediated by glia. Here, we show that primed microglia and astrocytes developed in mice 1 month following moderate diffuse TBI, coinciding with cognitive deficits that were not initially evident after injury. Additionally, TBI-induced glial priming may adversely affect the ability of glia to appropriately respond to immune challenges, which occur regularly across the lifespan. Indeed, we show that an acute immune challenge augmented microglial reactivity and cognitive deficits. This idea may provide new avenues of clinical assessments and treatments following TBI.     

A New Model for Posttraumatic Osteomyelitis in Rabbits

A new animal model for posttraumatic osteomyelitis was designed. This model mimics the pathogenesis of the human disease more accurately than models presently available. Femora of New Zealand white rabbits were exposed at the greater trochanter and a stainless steel rod was inserted into the marrow cavity. A Staphylococcus aureus suspension was placed in and around a bone defect, which was drilled midshaft. The disease was evaluated by clinical observation and roentgenographic, hematologic, bacteriologic, and histologic parameters. Osteomyelitis developed in all 24 infected rabbits. None of the five rabbits receiving only an intramedullary rod developed an osteomyelitis. This model proves that an experimental posttraumatic osteomyelitis associated with a foreign body can be reliably induced, even when no infection-promoting chemical agents, small inoculum of bacteria, or minimal bone trauma is present.     

Self-reported exposure to severe events on the labour ward among Swedish midwives and obstetricians: A cross-sectional retrospective study

BackgroundThe process of delivery entails potentially traumatic events in which the mother or child becomes injured or dies. Midwives and obstetricians are sometimes responsible for these events and can be negatively affected by them as well as by the resulting investigation or complaints procedure (clinical negligence).ObjectiveTo assess the self-reported exposure rate of severe events among midwives and obstetricians on the delivery ward and the cumulative risk by professional years and subsequent investigations and complaints.DesignCross-sectional survey.ParticipantsMembers of the Swedish Association of Midwives (SFB) and the Swedish Society of Obstetrics and Gynaecology (SFOG).MethodsA questionnaire covering demographic characteristics, experiences of self-reported severe events on the delivery ward, and complaints of medical negligence was developed. Potential consequences of the complaint was not reported. A severe event was defined as: 1) the death of an infant due to delivery-related causes during childbirth or while on the neonatal ward; 2) an infant being severely asphyxiated or injured at delivery; 3) maternal death; 4) very severe or life threatening maternal morbidity; or 5) other stressful events during delivery, such as exposure to violence or aggression.ResultsThe response rate was 39.9% (n = 1459) for midwives and 47.1% (n = 706) for obstetricians. Eighty-four percent of the obstetricians and almost 71% of responding midwives had experienced one or more self-reported severe obstetric event with detrimental consequences for the woman or the new-born. Fourteen percent of the midwives and 22.4% of the obstetricians had faced complaints of medical negligence from the patient or the family of the patient.ConclusionsA considerable proportion of midwives and obstetricians will, in the course of their working life, experience severe obstetric events in which the mother or the new-born is injured or dies. Preparedness for such exposure should be part of the training, as should managerial and peer support for those in need. This could prevent serious consequences for the health care professionals involved and their subsequent careers.     

Paediatric orthopaedic infections

Bone and joint infections in children are uncommon, but potentially devastating. The use of effective antibiotic chemotherapy has minimized associated mortality, but prompt recognition and treatment is necessary to preserve normal growth and function of the affected bone or joint. Diagnostic challenges include inability of patients to report symptoms, non-specificity of clinical signs and low sensitivity of diagnostic tests while treatment challenges include choosing appropriate empiric antibiotics, accounting for patient and epidemiological risk factors, and ensuring adequate compliance with long antibiotic courses in children. Successful management requires regular review of clinical progress and assessment for development of complications requiring surgical intervention. This article will cover the commonest infections seen clinically. Septic arthritis and osteomyelitis are discussed separately though concurrent infection can occur, particularly in children under 2 years of age, and recognition of this can alter the duration of treatment required.     

Case of localized scleroderma associated with osteomyelitis

We report a 4-year-old girl presenting with progressive linear scleroderma affecting the right leg. Biopsy specimen disclosed typical histopathological findings of localized scleroderma. Right leg magnetic resonance imaging (MRI) showed high signal areas on T₂-weighted images on the subcutaneous fatty tissue, muscles and bone marrow, suggesting that skin inflammation extended to the bone marrow. Oral corticosteroid therapy was instituted with improvement of both skin sclerosis and MRI findings. Our observations suggest that MRI examination should be considered in patients with localized scleroderma to evaluate the extension of the inflammation.     

The natural history of post-traumatic hypopituitarism: implications for assessment and treatment

Purpose

Hypopituitarism has been reported in up to half of long-term survivors of traumatic brain injury. We attempted to define the natural history of post-traumatic hypopituitarism to devise guidelines for the optimal timing of patients’ assessment and hormone replacement.

Subjects and methods

Fifty consecutive patients with severe or moderate head trauma were enrolled in a prospective study of pituitary function during the acute phase, at 6 months, and at 12 months after injury. Growth hormone and adrenocorticotropin hormone reserves were assessed using the glucagon stimulation test. Baseline serum concentrations of other anterior pituitary hormones were measured. Results were compared with normative data obtained from matched healthy controls.

Results

Nine patients (18%) had growth hormone deficiency in the acute phase; at 6 months, 5 patients recovered function and 2 new deficiencies were detected; at 12 months, 1 patient recovered, leaving 5 patients (10%) with growth hormone deficiency. Eight patients (16%) showed subnormal cortisol response in the acute phase; at 6 months, 4 patients had recovered and 5 new deficiencies were detected; all 9 patients had persistent abnormalities at 2 months. Forty patients (80%) had gonadotropin deficiency in the acute phase, of whom 29 (73%) recovered by 6 months and 34 (85%) recovered by 12 months. Thyrotropin deficiency was present in 1 patient in the acute phase, who recovered by 6 months; 1 new case was diagnosed at 6 months, which persisted at 12 months.

Conclusion

After traumatic brain injury, early neuroendocrine abnormalities are sometimes transient, whereas late abnormalities present during the course of rehabilitation. A follow-up strategy with periodic evaluation is a necessary part of the optimal care for patients with traumatic brain injury.